SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.
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DOI：
10.1126/science.abe8499
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发表时间：
2020-12-18
期刊：
影响因子：
--
通讯作者：
Baric RS
中科院分区：
文献类型：
--
作者：
Hou YJ;Chiba S;Halfmann P;Ehre C;Kuroda M;Dinnon KH 3rd;Leist SR;Schäfer A;Nakajima N;Takahashi K;Lee RE;Mascenik TM;Graham R;Edwards CE;Tse LV;Okuda K;Markmann AJ;Bartelt L;de Silva A;Margolis DM;Boucher RC;Randell SH;Suzuki T;Gralinski LE;Kawaoka Y;Baric RS
病毒在未感染人群中的大流行传播可以选择改变发病机制、毒力和/或传播性的突变。起源于中国的严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）的祖先形式现在已经在很大程度上被病毒刺突蛋白中含有突变D 614 G（Asp 614-to-Gly）的菌株所取代。Hou等人在人类细胞和动物模型的一系列实验中比较了新变体与祖先形式的特征。这种变异体在感染上呼吸道上皮细胞方面更好，并且比祖先病毒复制的数量更多。有证据表明，动物模型中的毒力发生了适度（如果有的话）的显著变化。因此，该病毒似乎已经进化为在人类中更大的传播性，而不是更大的致病性。这种突变使新的病毒变体更容易受到中和抗血清的影响，而不会改变目前正在开发的候选疫苗的效力。目前SARS-CoV-2的主要结构变体似乎是从祖先形式进化而来的，并增强了传播性。在全球严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）毒株中普遍存在天冬氨酸-614替换为甘氨酸（D 614 G）的情况，但其对病毒发病机制和传播性的影响仍不清楚。我们设计了一种含有这种取代的SARS-CoV-2变体。与原始野生型病毒相比，该变体在原代人气道上皮细胞中表现出更有效的感染、复制和竞争适应性，但保持相似的形态和体外中和特性。两种病毒感染人血管紧张素转换酶2（ACE 2）转基因小鼠和叙利亚仓鼠，导致呼吸道组织和肺部疾病的病毒滴度相似。然而，D 614 G变体在仓鼠中的传播速度明显更快，并且比野生型病毒显示出更高的竞争适应性。这些数据表明，D 614 G取代增强了SARS-CoV-2的感染性、竞争适应性和在原代人类细胞和动物模型中的传播。
Pandemic spread of a virus in naïe populations can select for mutations that alter pathogenesis, virulence, and/or transmissibility. The ancestral form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged from China has now been largely replaced by strains containing the mutation D614G (Asp614-to-Gly) in the viral spike protein. Hou et al. compared the characteristics of the new variant against the ancestral form in a series of experiments in human cells and animal models. The variant is better at infecting upper-airway epithelial cells and replicates in greater numbers than the ancestral virus. Evidence indicates modest, if any, significant changes to virulence in animal models. Therefore, the virus appears to have evolved for greater transmissibility in humans rather than for greater pathogenicity. The mutation renders the new virus variant more susceptible to neutralizing antisera without altering the efficacy of vaccine candidates currently under development. Science, this issue p. 1464 The current dominant structural variant of SARS-CoV-2 appears to have evolved from the ancestral form and enhances transmissibility. The spike aspartic acid–614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.
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影响因子：
64.5
作者：
Hou, Yixuan J.;Okuda, Kenichi;Baric, Ralph S.
通讯作者：
Baric, Ralph S.
影响因子：
3
作者：
Omotuyi, I. Olaposi;Nash, Oyekanmi;Okaiyeto, Kunle
通讯作者：
Okaiyeto, Kunle
影响因子：
30.3
作者：
Weissman D;Alameh MG;de Silva T;Collini P;Hornsby H;Brown R;LaBranche CC;Edwards RJ;Sutherland L;Santra S;Mansouri K;Gobeil S;McDanal C;Pardi N;Hengartner N;Lin PJC;Tam Y;Shaw PA;Lewis MG;Boesler C;Şahin U;Acharya P;Haynes BF;Korber B;Montefiori DC
通讯作者：
Montefiori DC
影响因子：
5.4
作者：
Rockx, Barry;Sheahan, Timothy;Baric, Ralph
通讯作者：
Baric, Ralph
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro